Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop.

ABSTRACT: Endocytosis enables neurons to internalize molecules, maintaining homeostasis and responsiveness. The neuronal membrane-associated periodic skeleton (MPS), an actin spectrin-based cytoskeletal lattice, is known to restrict clathrin-mediated endocytosis (CME) in axons, but its broader role in other neuronal compartments and endocytic pathways remains unclear. Here, we show that all four major endocytic pathways-CME, caveolin-, flotillin-, and fast endophilin-mediated endocytosis-are spatially gated by the MPS and occur exclusively within MPS-free "clearing" zones throughout all neuronal compartments. Disrupting the MPS broadly enhances both basal and ligand-induced endocytosis. We also identify a previously unknown feedback loop in which ligand-triggered endocytosis activates extracellular

SUBMITTER: Fei J 

PROVIDER: S-EPMC12893284 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature